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This article presents abstracts of research papers on allergy and asthma, which include the importance of recognizing vocal cord dysfunction in allergy and asthma, a case of delayed hypersensitivity to three thienopyridines and a study on anaphylaxis after intravenous amiodarone administration.

Premature children with bronchopulmonary dysplasia (BPD) encounter several health issues potentially affecting their health-related quality of life (HRQL). We aimed to determine agreement between children with BPD and their parent's HRQL assessments. Using Patient-Reported Outcomes Measurement Information System (PROMIS) assessment tools, we evaluated agreement and potential bias between parent proxy and child self-reports of the PROMIS-Scale-Global Health-7, the Psychological Stress Experiences Short Form (PSE), and the PROMIS-Profile-25. Fifty-eight child-parent dyads from the Indoor Air Quality and Respiratory Morbidity in Children with BPD study were included. Intraclass correlations (ICC) between child self-report and parent proxy report showed moderate agreement for the Relationships domain (0.44 [95% confidence interval (CI) 0.38-0.53]) and poor agreement for the rest of the Profile-25 dimensions (Mobility, Anxiety, Depression, Pain, and Fatigue; range: 0.05-0.29), Global Health-7 (0.32 [95% CI 0.24-0.48), and PSE (0.34 [95% CI 0.27-0.49]) T-scores. Parents systematically overestimated negative HRQL domains (Pain, Anxiety, or Depression) and underestimated positive domains (Mobility or Relationship). As children age, the child-parent agreement worsens., Conclusions: In school-aged children with BPD, agreement between parents and children on HRQL scales is poor to moderate. Caregivers are biased towards lower HRQL. When possible, HRQL should be assessed in the patient directly., What Is Known: • Children with chronic respiratory diseases often assess their own health related quality of life different than their caregiver would report for the child. • Recent data suggests that parent reported health related quality of life for children with BPD is similar to the normal population., What Is New: • There is a consistent bias for parents to report worse health related quality of life on the Patient Reported Outcomes Measurement Information System (PROMIS) standardized assessment than their school-aged children with BPD., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Widespread North American wildfires in 2023 led to exposure to ambient wildfire smoke outside of traditionally wildfire-prone regions. The objective was to evaluate levels of indoor air pollutants in relation to ambient wildfire smoke exposure in eastern Massachusetts. Using a real-time multipollutant sensor system in five Boston area households, this study assessed indoor fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), and total volatile organic compound concentrations (TVOC) two days before and during days of hazardous wildfire smoke exposure (smoke days). The relationship between ambient PM 2.5 from regulatory monitors and indoor PM 2.5 before and during smoke days was investigated by mixed effects linear regression. During smoke days and the preceding non-smoke days, median indoor PM 2.5 was 9.9 µg/m 3 and 3.5 µg/m 3 ( p  < 0.001), respectively; median NO 2 was 20.5 ppb and 18.4 ppb ( p  = 0.11); median TVOC was 6,715 µg/m 3 and 5,361 µg/m 3 ( p  = 0.35). A 1% increase in ambient PM 2.5 was associated with a 0.93% increase in indoor PM 2.5 on smoke days (95% CI, 0.54%-1.32%) and a 0.34% increase on non-smoke days (95% CI, 0.17%-0.66%), though interaction testing of smoke day status was not statistically significant ( p  = 0.14). In Northeastern US homes, indoor PM 2.5 increased significantly during ambient wildfire smoke exposure, which may reflect increased infiltration and increased indoor particle-generating activities during smoke days. Implications : This study reports on household exposure to wildfire smoke in eastern Massachusetts, finding that indoor PM 2.5 more than doubled compared to preceding non-smoke days, while indoor NO 2 and TVOC did not significantly rise. Though the generalizability of this study is limited by the small number of homes studied, the findings suggest that more investigation is needed to understand indoor air pollution during future wildfire smoke exposure in regions not traditionally wildfire-prone and to inform mitigation efforts.

Background and Objectives: The lung and sleep health of adults is heavily influenced by early factors, both genetic and environmental; therefore, optimizing respiratory health begins in childhood. Multiple barriers impede improvements in lung and sleep health for children. First, the traditional siloing between general pediatric care in the community, pediatric pulmonary and sleep subspecialty care, and the research community limits the translation of knowledge into practice. Additionally, identifying and addressing health disparities remains a challenge. The 2021 NHLBI-sponsored workshop "Defining and Promoting Pediatric Pulmonary Health (DAP 3 H)" was a first step in defining critical gaps in our current healthcare system in identifying and optimizing lung and sleep health in children. The workshop identified key opportunities including measuring pulmonary function in young children, sleep-focused outcomes, developing biomarkers, and longitudinal research cohorts. To expand on the work of DAP 3 H and continue initiatives to improve childhood lung and sleep health, the Pediatrics & Pulmonary Network: Improving Health Together conference was held in 2023., Study Design: A modified Delphi process was applied to form consensus surrounding gaps, barriers, and action items, with the goal of identifying the most urgent opportnities for improving childhood lung and sleep health., Results: Cross-cutting foundational principles were identified as: (1) Authentic Stakeholder Collaboration & Engagement, (2) Reach & Implementation in Real World Settings, (3) Understanding Current Landscape & Resources and (4) Purposeful Diversity, Equity, & Inclusion Initiatives., Conclusions: To improve lung and sleep health in children, these principles should be the foundation for research design, development, and implementation., (© 2024 Wiley Periodicals LLC.)

Objective: Acid blocker therapy (ABT) has become common in cystic fibrosis (CF), despite insufficient evidence for benefits and studies showing potentially negative effects. We examined associations between ABT usage and growth, gut microbiome (GM), and early-onset lung disease in young children with CF., Methods: One hundred forty-five infants with CF born during 2012-2017, diagnosed through newborn screening by age 3 months and followed to 36 months of age at six CF centers were evaluated. Longitudinal data on growth, pancreatic functional status, pulmonary symptoms, and acid blocker medications were prospectively collected. Early-onset lung disease severity was evaluated by a clinical scoring system. GM composition was assessed by 16S rRNA methodology., Results: ABT use before age 3 years was frequent, with 81 (56%) of patients on H2 receptor antagonist (H2RA) or proton pump inhibitor (PPI), and higher among pancreatic insufficient (60%) versus pancreatic sufficient (26%) children. H2RA was commonly prescribed in infancy before transitioning to PPI. Growth improvements were not significantly greater, while GM α-diversity at 3 years of age was significantly lower and early-onset lung disease more severe, in persistent ABT users compared to nonusers of ABT., Conclusion: In our cohort of young children with CF, early and persistent ABT use was not associated with significant growth benefits and instead showed associations with reduced GM diversity and negative effects on early-onset lung disease. Consequentially, there is a critical need for systematic evaluation and comprehensive risk-benefit analysis of ABT to ensure proper guidelines for children with CF., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: In the United States, Black and Latino children with asthma are more likely than White children with asthma to require emergency department visits or hospitalizations because of an asthma exacerbation. Although many cite patient-level socioeconomic status and access to health care as primary drivers of disparities, there is an emerging focus on a major root cause of disparities-systemic racism. Current conceptual models of asthma disparities depict the historical and current effects of systemic racism as the foundation for unequal exposures to social determinants of health, environmental exposures, epigenetic factors, and differential healthcare access and quality. These ultimately lead to biologic changes over the life course resulting in asthma morbidity and mortality. Methods: At the 2022 American Thoracic Society International Conference, a diverse panel of experts was assembled to identify gaps and opportunities to address systemic racism in childhood asthma research. Panelists found that to examine and address the impacts of systemic racism on children with asthma, researchers and medical systems that support biomedical research will need to 1 ) address the current gaps in our understanding of how to conceptualize and characterize the impacts of systemic racism on child health, 2 ) design research studies that leverage diverse disciplines and engage the communities affected by systemic racism in identifying and designing studies to evaluate interventions that address the racialized system that contributes to disparities in asthma health outcomes, and 3 ) address funding mechanisms and institutional research practices that will be needed to promote antiracism practices in research and its dissemination. Results: A thorough literature review and expert opinion discussion demonstrated that there are few studies in childhood asthma that identify systemic racism as a root cause of many of the disparities seen in children with asthma. Community engagement and participation in research studies is essential to design interventions to address the racialized system in which patients and families live. Dissemination and implementation studies with an equity lens will provide the multilevel evaluations required to understand the impacts of interventions to address systemic racism and the downstream impacts. To address the impacts of systemic racism and childhood asthma, there needs to be increased training for research teams, funding for studies addressing research that evaluates the impacts of racism, funding for diverse and multidisciplinary research teams including community members, and institutional and financial support of advocating for policy changes based on study findings. Conclusions: Innovative study design, new tools to identify the impacts of systemic racism, community engagement, and improved infrastructure and funding are all needed to support research that will address impacts of systemic racism on childhood asthma outcomes.

Background: Dupilumab is the first and only biologic agent approved for the treatment of atopic dermatitis (AD) in pediatric patients aged from 6 months to 17 years. The study aimed to evaluate the impact of dupilumab on the occurrence of comorbidities in pediatric patients with AD., Methods: In this population-based cohort study, we utilized electronic health records from multiple healthcare organizations across the United States. Pediatric patients (<18 years of age) with a diagnosis of AD initiating dupilumab were propensity-score matched 1:1 to those initiating other systemic agents (azathioprine, cyclosporine, methotrexate, mycophenolate mofetil, or systemic corticosteroids). The primary outcomes were new-onset comorbidities emerging during the study period measured by the risk ratio (RR) and its confidence interval (CI). Subgroup analyses were stratified by age (0-5 years, 6-11 years, and 12-17 years), sex, and race., Results: A total of 3575 pediatric patients with AD treated with dupilumab were matched to 3575 patients treated with other systemic agents. The dupilumab cohort was associated with a lowered risk of new-onset atopic comorbidities (including asthma [RR, 0.72; 95% CI, 0.59-0.89] and allergic rhinitis [RR, 0.62; 95% CI, 0.52-0.74]), infections (e.g., skin and soft tissue infection [RR, 0.70; 95% CI, 0.63-0.76] and respiratory tract infection [RR = 0.56; 95% CI, 0.51-0.61]), psychiatric disorders (e.g., mood disorder [RR, 0.52; 95% CI, 0.39-0.70] and anxiety [RR, 0.57; 95% CI, 0.46-0.70], sleep disturbance [RR, 0.60; 95% CI, 0.47-0.77]), neurologic and developmental disorders (e.g., attention deficit hyperactivity disorder [RR, 0.54; 95% CI, 0.38-0.75]). Furthermore, the positive effects are found to be more pronounced in younger children (aged 0-5 years) with AD., Conclusions: Treatment with dupilumab compared to systemic agents resulted in reductions in AD-related comorbidities in pediatric patients., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: The burden of pediatric asthma and other allergic diseases is not evenly distributed among United States populations., Objective: To determine whether urinary biomarkers are associated with asthma morbidity, and if associations vary by child race, ethnicity and sex., Methods: This study includes n = 152 children with physician-diagnosed asthma who participated in the School Inner-City Asthma Intervention Study (SICAS-2). Metabolites of phenol, paraben, polycyclic aromatic hydrocarbons, and phthalate analytes were analyzed from urine samples collected at baseline. Asthma symptom days over the past 2 weeks were dichotomized to no asthma symptom days or any asthma symptom days. Cross-sectional regression models were adjusted for age, sex, number of colds, household income, prescription control, race and ethnicity, body mass index (BMI) percentile, and smoke exposure. Weighted quantile sum regression was used to analyze each chemical class and a total mixture effect, controlling for the same covariates. Analyses were conducted with the assistance of the National Institute of Environmental Health Sciences Children's Health Exposure Analysis Resource (CHEAR)., Results: Participants were mostly Hispanic/Latino and low income with an average age of 7.83 years and the average maximum asthma symptom days over the past two weeks of 2.13 (standard deviation: 3.56). The maximum concentrations indicate extreme values for several chemicals, including bisphenol-3, 2,5-dichlorophenol, propyl and methyl parabens, triclosan, methyl paraben and cotinine. We found a significant interaction effect and differing contributions of analytes for children with allergen sensitivity versus those that did not. For stratified analyses assessing effect modification by child race and ethnicity, weighted quantile sum interaction models showed reduced odds of asthma symptoms to a greater magnitude in children of other races and ethnicities compared to Black, Non-Hispanic children., Conclusions: Preliminary analyses of the association between environmental chemical exposure and asthma symptoms among inner-city children revealed an inverse association, which may be due to personal care and medication use and can be understood further in future analyses. Beneficial effects were detected for most of the chemicals., (Copyright © 2024. Published by Elsevier GmbH.)

Background: Since there are known adverse health impacts of traffic-related air pollution, while at the same time there are potential health benefits from greenness, it is important to examine more closely the impacts of these factors on indoor air quality in urban schools., Objective: This study investigates the association of road proximity and urban greenness to indoor traffic-related fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), and black carbon (BC) in inner-city schools., Methods: PM 2.5 , NO 2 , and BC were measured indoors at 74 schools and outdoors at a central urban over a 10-year period. Seasonal urban greenness was estimated using the Normalized Difference Vegetation Index (NDVI) with 270 and 1230 m buffers. The associations between indoor traffic-related air pollution and road proximity and greenness were investigated with mixed-effects models., Results: The analysis showed linear decays of indoor traffic-related PM 2.5 , NO 2 , and BC by 60%, 35%, and 22%, respectively for schools located at a greater distance from major roads. The results further showed that surrounding school greenness at 270 m buffer was significantly associated (p < 0.05) with lower indoor traffic-related PM 2.5 : -0.068 (95% CI: -0.124, -0.013), NO 2 : -0.139 (95% CI: -0.185, -0.092), and BC: -0.060 (95% CI: -0.115, -0.005). These associations were stronger for surrounding greenness at a greater distance from the schools (buffer 1230 m) PM 2.5 : -0.101 (95% CI: -0.156, -0.046) NO 2 : -0.122 (95% CI: -0.169, -0.075) BC: -0.080 (95% CI: -0.136, -0.026). These inverse associations were stronger after fully adjusting for regional pollution and meteorological conditions., Impact Statement: More than 90% of children under the age of 15 worldwide are exposed to elevated air pollution levels exceeding the WHO's guidelines. The study investigates the impact that urban infrastructure and greenness, in particular green areas and road proximity, have on indoor exposures to traffic-related PM 2.5 , NO 2 , and BC in inner-city schools. By examining a 10-year period the study provides insights for air quality management, into how road proximity and greenness at different buffers from the school locations can affect indoor exposure., (© 2024. The Author(s).)

Purpose of Review: Ubiquitous environmental exposures, including ambient air pollutants, are linked to the development and severity of childhood asthma. Advances in our understanding of these links have increasingly led to clinical interventions to reduce asthma morbidity., Recent Findings: We review recent work untangling the complex relationship between air pollutants, including particulate matter, nitrogen dioxide, and ozone and asthma, such as vulnerable windows of pediatric exposure and their interaction with other factors influencing asthma development and severity. These have led to interventions to reduce air pollutant levels in children's homes and schools. We also highlight emerging environmental exposures increasingly associated with childhood asthma. Growing evidence supports the present threat of climate change to children with asthma. Environmental factors play a large role in the pathogenesis and persistence of pediatric asthma; in turn, this poses an opportunity to intervene to change the course of disease early in life., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Asthma is the most common chronic disease among children. Asthma Action Plans (AAPs) enable asthma self-management tailored to each patient and should be updated annually. At our institution, providers face challenges in creating reliable processes to consistently complete AAPs for patients with asthma. This project's aim was to increase the percentage of patients across five hospital divisions who have an up-to-date AAP from 80% in May 2021 to 85% by October 1, 2021., Methods: We launched a quality improvement (QI) project using the Model for Improvement, focusing on improving AAP completion rates across five hospital divisions providing ambulatory care for asthma patients. The divisions (Adolescent/Young Adult Medicine, Allergy, Pulmonary, and two Primary Care sites) participated in the QI process using tools to understand the problem context. They implemented a cross-divisional AAP completion competition from June to October 2021. Each month during Action Periods, divisions trialed their interventions using Plan-Do-Study-Act cycles. We held monthly Learning Sessions for divisions to collaborate on successful intervention strategies., Results: Statistical process control chart analysis demonstrated that the overall AAP completion rate increased from a baseline of 80% to 87% with the initiation of the competition. All divisions showed improvement in AAP completion rates during the active intervention period, but sustainment varied., Conclusions: The cross-divisional competition motivated five divisions to improve processes to increase AAP completion rates. This approach effectively fostered engagement and idea sharing to boost performance, and may be considered for other QI projects., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: No previous study has evaluated the relationship between chronotype and adherence to the Mediterranean diet among adolescents. The aim of the present study was to assess the association between chronotype and adherence to the Mediterranean diet in a sample of Spanish adolescents aged 12-17 years., Methods: This study examined secondary data from 820 adolescents (55.5% girls) from the Eating Healthy and Daily Life Activities (EHDLA) study, which included a representative sample of adolescents aged 12-17 years from the Valle de Ricote (Region of Murcia, Spain). Adolescents' chronotype was evaluated with the Morningness/Eveningness Scale in Children. Adherence to the Mediterranean diet was determined through the Mediterranean Diet Quality Index for Children and Teenagers., Results: The proportion of adolescents with an optimal Mediterranean diet was 37.6%. In relation to chronotype, we found that 24.5%, 69.4%, and 6.1% of the adolescents were classified as morning, intermediate, and evening types, respectively. After adjusting for several covariates, both evening- and intermediate-type adolescents showed lower odds of having optimal adherence to the Mediterranean diet (evening-type: odds ratio [OR] = 0.30, confidence interval [CI] 95% 0.12-0.72; intermediate-type: OR = 0.62, CI 95% 0.44-0.87) than morning-type adolescents., Conclusions: Chronotype could affect adherence to the Mediterranean Diet in adolescents, so it should be a factor to be considered in future studies assessing eating habits., Impact: No previous study has evaluated the relationship between chronotype and adherence to the Mediterranean diet among adolescents. Both evening- and intermediate-type adolescents showed lower odds of having optimal Mediterranean diet adherence than morning-type adolescents. These findings may indicate a need to promote eating healthy habits based on a more holistic approach, not only on the total energy expenditure or in specific food groups but also on the chronotype., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objective: To determine health-related quality of life (HRQOL) of school-aged children with bronchopulmonary dysplasia (BPD) using the standardized Patient-Reported Outcomes Measurement Information System (PROMIS) assessment tools., Study Design: The Indoor Air Quality and Respiratory Morbidity in Children with BPD Study is an ongoing observational study of school-aged children with BPD. HRQOL is assessed at enrollment by 3 PROMIS questionnaires, Parent Proxy Scale-Global Health 7, Parent Proxy Psychological Stress Experiences-Short Form, and the Parent Proxy Profile-Profile-25. PROMIS data were tested for significant deviation from the standardized T-Score references for normative populations of children., Results: Eighty-nine subjects enrolled in the AERO-BPD study had complete outcome data for HRQOL. The mean age was 9 (±2) years and 43% were female. Mean days on respiratory support totaled 96 (±40). Across all domains, school-aged children with BPD reported similar or slightly better outcomes than the reference sample. Statistically significant findings of lower depression (P < .0001), fatigue (P < .0001), and pain (P < .0001) scores were found; there was no difference in psychological stress experiences (P = .87), global health (P = .06), anxiety (P = .08), relationships (P = .80), and mobility (P = .59) domains., Conclusions: This study demonstrated that children with BPD may have less depression, fatigue, and pain HRQL than the general population. Once validated, these findings may offer reassurance to parents and providers caring for children with BPD., Competing Interests: Declaration of Competing Interest This research was funded by the National Institute of Environmental Health Sciences (NIEHS) (Grant Number R01ES030100 [to J.G.]). This work was conducted with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health (NIH) Award UL1 TR002541) and financial contributions from Harvard University and its affiliated academic health care centers [to G.S.]. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health. J.G. receives research funding from the NIH, Vertex Pharmaceuticals, and consulting fees from AiCME (for medical education). He has no conflicts of interest related to the material in this manuscript. All other authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Data on the use of remote spirometry are limited in the pediatric population. We sought to assess the feasibility and accuracy of a digital turbine spirometer, Medical International Research (MIR) Spirobank Smart (MIR, New Berlin, WI, USA), compared with a pneumotachography spirometer, Pneumotrac (Vitalograph Inc., Lenexa, KS, USA), in field-based clinical research. Methods: This is a cross-sectional study of a subgroup of school-aged participants enrolled in the Air quality, Environment, and Respiratory Outcomes in Bronchopulmonary Dysplasia (BPD) study, who performed same-day paired coached baseline spirometry measurements from the Pneumotrac and MIR devices. Proportion of successful tests was estimated for each device and compared using McNemar's test. Correlation between devices forced expiratory volume in 1 second (FEV 1 ) and forced vital capacity (FVC) was analyzed by Lin's concordance correlation, and Bland-Altman plots were generated. Results: Twenty-one participants with history of BPD completed home spirometry maneuvers on both devices. The mean age of participants was 8.7 years. The mean FEV 1 and FVC measurement was 81% predicted and 90.4% predicted, respectively. The proportion of acceptable tests appeared higher using Pneumotrac (81%) than when using MIR (67%), although without evidence of discordance ( P  = 0.317). Among subjects with successful tests on both devices, Lin's concordance correlation demonstrated moderate agreement (FEV 1 r  = 0.955, 95% confidence interval [CI]: 0.87-0.98; FVC r  = 0.971, CI: 0.91-0.99). The mean difference in FEV 1 between Pneumotrac and MIR was 0.079 L (95% limits of agreement were -0.141 to 0.298 L) and FVC was 0.075 L (95% limits of agreement were -0.171 to 0.322 L). These were relatively small and without evidence of systematic or volume-dependent bias. Conclusions: Utilizing turbine spirometers may be a promising and feasible way to perform pulmonary function testing for field research in children.

Lifelong respiratory health is rooted in the structural and functional development of the respiratory system in early life. Exposures and interventions antenatally through childhood can influence lung development into young adulthood, the life stage with the highest achievable lung function. Because early respiratory health sets the stage for adult lung function trajectories and risk of developing chronic obstructive pulmonary disease, understanding how to promote lung health in children will have far reaching personal and population benefits. To achieve this, it is critical to have accurate and precise measures of structural and functional lung development that track throughout life stages. From this foundation, evaluation of environmental, genetic, metabolic, and immune mechanisms involved in healthy lung development can be investigated. These goals require the involvement of general pediatricians, pediatric subspecialists, patients, and researchers to design and implement studies that are broadly generalizable and applicable to otherwise healthy and chronic disease populations. This National Institutes of Health workshop report details the key gaps and opportunities regarding lung function and structure., (Copyright © 2023 by the American Academy of Pediatrics.)

Background: Radon may have a role in obstructive lung disease outside its known carcinogenicity. Little is known about radon's effects on asthma morbidity., Objective: To determine the effect of radon on fractional exhaled nitric oxide (F E NO), asthma symptom-days, and lung function in inner-city asthmatic school children., Methods: Two hundred ninety-nine school-aged asthmatic children enrolled in the School Inner-City Asthma Study (SICAS-1) were followed. One and two-month averaged radon was assessed using a spatiotemporal model predicting zip code-specific monthly exposures. F E NO and spirometry were measured twice during the academic year. Asthma symptoms were assessed four times during the academic year. The interaction between indoor radon exposure (Bq/m 3 ) and seasonality predicting log-transformed F E NO, forced expiratory volume in 1 s (FEV 1 ) % predicted, forced vital capacity (FVC) % predicted, FEV 1 /FVC, and asthma symptom-days was evaluated., Results: Participants with high radon exposure had greater change in F E NO from warm to cold periods compared to low radon exposure (interaction p = 0.0013). Participants with >50th percentile radon exposure experience significant F E NO increase from warm to cold weather ( β $\beta $  = 0.29 [95% confidence interval [CI]: 0.04-0.54], p = 0.0240). We report a positive association between radon 1-month moving average (incidence rate ratio [IRR] = 1.01, p = 0.0273) and 2-month moving average (IRR = 1.01, p = 0.0286) with maximum asthma symptom-days (n = 299, obs = 1167)., Conclusions: In asthmatic children, radon may be associated with increased asthma morbidity, suggesting radon may be a modifiable environmental risk factor for airway inflammation., (© 2023 Wiley Periodicals LLC.)

Purpose of Review: The current review provides an assessment of the recent pediatric literature evaluating socioeconomic drivers of asthma incidence and morbidity. The review addresses the specific social determinants of health related to housing, indoor and outdoor environmental exposures, healthcare access and quality, and the impact of systematic racism., Recent Findings: Many social risk factors are associated with adverse asthma outcomes. Children living in low-income, urban neighborhoods have greater exposure to both indoor and outdoor hazards, including molds, mice, second-hand smoke, chemicals, and air pollutants, all of which are associated with adverse asthma outcomes. Providing asthma education in the community - via telehealth, school-based health centers, or peer mentors - are all effective methods for improving medication adherence and asthma outcomes. The racially segregated neighborhoods created by the racist 'redlining' policies implemented decades ago, persist today as hotspots of poverty, poor housing conditions, and adverse asthma outcomes., Summary: Routine screening for social determinants of health in clinical settings is important to identify the social risk factors of pediatric patients with asthma. Interventions targeting social risk factors can improve pediatric asthma outcomes, but more studies are needed related to social risk interventions., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Higher asthma prevalence and morbidity are seen in inner-city areas, disproportionately affecting low-income families living in substandard housing. Children within these families experience more frequent asthma exacerbations, acute care and emergency department visits, and hospitalizations, thus characterizing severe asthma. In this review, we assess recent published literature focused on indoor and outdoor exposures that contribute to the development and morbidity of asthma., Recent Findings: Many urban environmental exposures contribute to asthma burden, including tobacco/e-cigarette smoke, pest allergens, molds, and possibly synthetic chemicals such as phthalates and bisphenol A, radon, and volatile organic compounds. Individuals living in inner-city areas also experience higher levels of air pollutants and ambient heat, further perpetuating asthma incidence and severity., Summary: This article summarizes the latest advances and provides direction for future research on risk factors, interventions, and public policy to help alleviate the burden of asthma due to urban environment exposures., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Asthma is the most common chronic disease of childhood. Environmental exposures, such as allergens and pollutants, are ubiquitous factors associated with asthma development and asthma morbidity. In this review, we highlight the most recent studies relevant to childhood asthma risk, onset, and exacerbation related to air pollution exposure., Recent Findings: In this article, we review current research that has been published between 2021 and 2022, demonstrating the effects of early-life exposure to key air pollutants (e.g., particulate matter (PM), nitrogen dioxide (NO 2 ), sulfur dioxide (SO 2 ) and ground-level ozone (O 3 ), environmental tobacco smoke, radon, and volatile organic compounds (VOC) on respiratory health., Summary: Air pollution continues to be a global burden with serious consequences related to respiratory health. Interventions aimed at reducing air pollution in the environment must be achieved in an effort to improve asthma outcomes and pediatric health., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The School Inner-City Asthma Intervention Study 2 (SICAS 2) tested interventions to reduce exposures in classrooms of students with asthma. The objective of this post-hoc analysis was limited to evaluating the effect of high-efficiency particulate (HEPA) filtration interventions on mold levels as quantified using the Environmental Relative Moldiness Index (ERMI) and the possible improvement in the students' asthma, as quantified by spirometry testing., Methods: Pre-intervention dust samples were collected at the beginning of the school year from classrooms and corresponding homes of students with asthma ( n  = 150). Follow-up dust samples were collected in the classrooms at the end of the HEPA or Sham intervention. For each dust sample, ERMI values and the Group 1 and Group 2 mold levels (components of the ERMI metric) were quantified. In addition, each student's lung function was evaluated by spirometry testing, specifically the percentage predicted forced expiratory volume at 1 sec (FEV1%), before and at the end of the intervention., Results: For those students with a higher Group 1 mold level in their pre-intervention classroom than home ( n  = 94), the FEV1% results for those students was significantly ( p  < 0.05) inversely correlated with the Group 1 level in their classrooms. After the HEPA intervention, the average Group 1 and ERMI values were significantly lowered, and the average FEV1% test results significantly increased by an average of 4.22% for students in HEPA compared to Sham classrooms., Conclusions: HEPA intervention in classrooms reduced Group 1 and ERMI values, which corresponded to improvements in the students' FEV1% test results.

Background: Children with asthma are at risk for low lung function extending into adulthood, but understanding of clinical predictors is incomplete., Objective: We sought to determine phenotypic factors associated with FEV 1 throughout childhood in the Severe Asthma Research Program 3 pediatric cohort., Methods: Lung function was measured at baseline and annually. Multivariate linear mixed-effects models were constructed to assess the effect of baseline and time-varying predictors of prebronchodilator FEV 1 at each assessment for up to 6 years. All models were adjusted for age, predicted FEV 1 by Global Lung Function Initiative reference equations, race, sex, and height. Secondary outcomes included postbronchodilator FEV 1 and prebronchodilator FEV 1 /forced vital capacity., Results: A total of 862 spirometry assessments were performed for 188 participants. Factors associated with FEV 1 include baseline Feno (B, -49 mL/log 2 PPB; 95% CI, -92 to -6), response to a characterizing dose of triamcinolone acetonide (B, -8.4 mL/1% change FEV 1 posttriamcinolone; 95% CI, -12.3 to -4.5), and maximal bronchodilator reversibility (B, -27 mL/1% change postbronchodilator FEV 1 ; 95% CI, -37 to -16). Annually assessed time-varying factors of age, obesity, and exacerbation frequency predicted FEV 1 over time. Notably, there was a significant age and sex interaction. Among girls, there was no exacerbation effect. For boys, however, moderate (1-2) exacerbation frequency in the previous 12 months was associated with -20 mL (95% CI, -39 to -2) FEV 1 at each successive year. High exacerbation frequency (≥3) 12 to 24 months before assessment was associated with -34 mL (95% CI, -61 to -7) FEV 1 at each successive year., Conclusions: In children with severe and nonsevere asthma, several clinically relevant factors predict FEV 1 over time. Boys with recurrent exacerbations are at high risk of lower FEV 1 through childhood., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Because of the heterogeneity in cystic fibrosis (CF) lung disease among young children, a clinical method to identify early-onset lung disease is needed., Objective: To develop a CF early-onset lung disease (CFELD) scoring system by utilizing prospectively collected longitudinal data on manifestations in the first 3 years of life., Design: We studied 145 infants born during 2012-2017, diagnosed through newborn screening by age 3 months, and followed to 36 months of age. Cough severity, pulmonary exacerbations (PEx), respiratory cultures, and hospitalizations were collected at each CF center visit (every 1-2 months in infancy and quarterly thereafter). These data were used to construct the CFELD system and to classify lung disease into five categories: asymptomatic, minimal, mild, moderate, and severe., Results: The most frequent manifestation of CF early lung disease was MD-reported PEx episodes, PEx hospitalizations, and positive Pseudomonas aeruginosa cultures. Parent-reported cough severity was correlated with the number of respiratory hospitalizations (r = 0.48, p < 0.0001). The distribution of CFELD categories was 10% asymptomatic, 17% minimal, 29% mild, 33% moderate, and 12% severe. The moderate and severe categories occurred threefold higher in pancreatic insufficient (PI, 49%) versus sufficient subjects (16%), p < 0.0001. In addition to PI, gastrointestinal and nutrition-related hospitalizations, plasma cytokines interleukin (IL)-6 and IL-10, duration of CFTR modulator therapy, and type of health insurance were significant predictors of CFELD scores., Conclusion: The CFELD scoring system is novel, allows systematic evaluation of lung disease prognosis early, and may aid in therapeutic decision-making particularly in the initiation of CFTR modulator therapy., (© 2022 Wiley Periodicals LLC.)

Objective: Children with severe asthma are underrepresented in studies of the relationship of sleep-disordered breathing (SDB) and asthma and little is known about sex differences of these relationships. We sought to determine the relationship of SDB with asthma control and lung function among boys and girls within a pediatric severe asthma cohort., Methods: Patients attending clinic visits at the Boston Children's Hospital Pediatric Severe Asthma Program completed the Pediatric Sleep Questionnaire (PSQ), Asthma Control Test (ACT) and Spirometry. The prevalence of SDB was defined as a PSQ score >0.33. We analyzed the association between PSQ score and both ACT score and spirometry values in mixed effect models, testing interactions for age and sex., Results: Among 37 subjects, mean age was 11.8 years (4.4) and 23 (62.2%) were male, the prevalence of SDB was 43.2% (16/37). Including all 80 observations, there was a moderate negative correlation between PSQ and ACT scores (r=-0.46, p  < 0.001). Multivariable linear regression models revealed a significant sex interaction with PSQ on asthma control ( p  = 0.003), such that for each 0.10 point increase in PSQ there was a 1.88 point decrease in ACT score for females but only 0.21 point decrease in ACT score for males. A positive PSQ screen was associated with a 9.44 point (CI 5.54, 13.34, p  < 0.001) lower ACT score for females and a 3.22 point (CI 0.56, 5.88, p  = 0.02) lower score for males., Conclusions: SDB is common among children with severe asthma. Among children with severe asthma, SDB in girls portends to significantly worse asthma control than boys., Supplemental data for this article is available online at https://doi.org/10.1080/02770903.2021.1897838.

Background: School classrooms, where students spend the majority of their time during the day, are the second most important indoor microenvironment for children., Objective: We investigated factors influencing classroom exposures to fine particulate matter ( PM 2.5 ), black carbon (BC), and nitrogen dioxide ( NO 2 ) in urban schools in the northeast United States., Methods: Over the period of 10 y (2008-2013; 2015-2019) measurements were conducted in 309 classrooms of 74 inner-city schools during fall, winter, and spring of the academic period. The data were analyzed using adaptive mixed-effects least absolute shrinkage and selection operator (LASSO) regression models. The LASSO variables included meteorological-, school-, and classroom-based covariates., Results: LASSO identified 10, 10, and 11 significant factors ( p < 0.05 ) that were associated with indoor PM 2.5 , BC, and NO 2 exposures, respectively. The overall variability explained by these models was R 2 = 0.679 , 0.687, and 0.621 for PM 2.5 , BC, and NO 2 , respectively. Of the model's explained variability, outdoor air pollution was the most important predictor, accounting for 53.9%, 63.4%, and 34.1% of the indoor PM 2.5 , BC, and NO 2 concentrations. School-based predictors included furnace servicing, presence of a basement, annual income, building type, building year of construction, number of classrooms, number of students, and type of ventilation that, in combination, explained 18.6%, 26.1%, and 34.2% of PM 2.5 , BC, and NO 2 levels, whereas classroom-based predictors included classroom floor level, classroom proximity to cafeteria, number of windows, frequency of cleaning, and windows facing the bus area and jointly explained 24.0%, 4.2%, and 29.3% of PM 2.5 , BC, and NO 2 concentrations, respectively., Discussion: The adaptive LASSO technique identified significant regional-, school-, and classroom-based factors influencing classroom air pollutant levels and provided robust estimates that could potentially inform targeted interventions aiming at improving children's health and well-being during their early years of development. https://doi.org/10.1289/EHP10007.

Asthma is among the most common medical conditions affecting children and young people, with adolescence a recognised period of increased risk, overrepresented in analyses examining recent increasing asthma mortality rates. Asthma may change significantly during this period and management also occurs in the context of patients seeking increased autonomy and self-governance whilst navigating increasing academic and social demands. A number of disease factors can destabilise asthma during adolescence including: increased rates of anaphylaxis, anxiety, depression, obesity, and, in females, an emerging resistance to corticosteroids and the pro-inflammatory effects of oestrogen. Patient factors such as smoking, vaping, poor symptom recognition, treatment non-adherence and variable engagement with health services contribute to difficult to treat asthma. Significant deficiencies in the current approach to transition have been identified by a recent EAACI task force, and subsequent asthma-specific recommendations, published in 2020 provide an important framework moving forward. As with other chronic conditions, effective transition programmes plan ahead, engage with adolescents and their families to identify the patients' management priorities and the current challenges they are experiencing with treatment. Transition needs may vary significantly across asthma patients and for more complex asthma may include dedicated transition clinics involving multidisciplinary care requiring input including, amongst others, allergy and immunology, psychological medicine, respiratory physicians and scientists and nurse specialists. Across different global regions, barriers to treatment may vary but need to be elicited and an individualised approach taken to optimising asthma care which is sustainable within the local adult healthcare system., (Copyright © 2021. Published by Elsevier Ltd.)

Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation-prone asthma, who contribute disproportionately to disease burden. Extensive deep phenotyping has revealed the heterogeneous nature of severe asthma and identified distinct disease subtypes. A current challenge in the field is to translate new and emerging knowledge about different pathobiologic mechanisms in asthma into patient-specific therapies, with the ultimate goal of modifying the natural history of disease. Here, we describe the Precision Interventions for Severe and/or Exacerbation-Prone Asthma (PrecISE) Network, a groundbreaking collaborative effort of asthma researchers and biostatisticians from around the United States. The PrecISE Network was designed to conduct phase II/proof-of-concept clinical trials of precision interventions in the population with severe asthma, and is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Using an innovative adaptive platform trial design, the PrecISE Network will evaluate up to 6 interventions simultaneously in biomarker-defined subgroups of subjects. We review the development and organizational structure of the PrecISE Network, and choice of interventions being studied. We hope that the PrecISE Network will enhance our understanding of asthma subtypes and accelerate the development of therapeutics for severe asthma., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The Hospital Asthma Severity Score (HASS) was developed to communicate inpatient asthma severity between providers. The purpose of this prospective study was to validate the HASS against the Pediatric Respiratory Assessment Measure (PRAM) and spirometry for assessment of inpatient asthma exacerbation severity in patients 2-18 years old, at a single point-in-time., Methods: This study was registered with clinicaltrials.gov (NCT02782065). Children admitted to a tertiary care, free-standing children's hospital were assessed for asthma severity using the HASS, PRAM, and pulmonary function by spirometry. Inter-rater agreement of HASS and PRAM scores was assessed between two blinded clinician raters. Spirometry results were obtained by a certified pulmonary laboratory technician and correlated with HASS and PRAM scores., Results: The sample included 58 subjects. Allowing for a one-point difference in continuous HASS and PRAM scores, inter-rater agreement was 79% for the HASS and 60% for the PRAM. When the scores were categorized as mild, moderate, and severe, inter-rater agreement was 62% for the HASS and 93% for the PRAM ( p < .0001). Additionally, intra-rater agreement between HASS and PRAM severity categories was 71% for Rater 1 and 64% for Rater 2. A weak correlation was noted between both the HASS and FEV 1 (r = -0.31; p  = 0.11), and PRAM and FEV 1 (r = -0.30; p  = 0.11) for the 29 subjects with acceptable spirometry results., Conclusions: The HASS and PRAM have acceptable inter-rater and intra-rater agreement. These results support validation of the HASS for managing hospitalized patients during asthma exacerbations.

Assessment of asthma comorbidities, conditions that adversely affect the pathobiology of asthma or impair its response to therapies, is a fundamental step in the evaluation and management of patients with difficult-to-treat asthma. Identifying and effectively treating asthma comorbidities, such as obesity, obstructive sleep apnea, and chronic sinusitis with nasal polyps, may improve asthma control and reduce exacerbations. In addition, identifying comorbid T2 inflammatory conditions may help guide optimal selection of biologic therapies. Here, we describe common comorbid conditions found in adult and pediatric difficult-to-control asthma, discuss evidence for the association with asthma morbidity and treatment benefit, and provide information on how and when to assess comorbidities., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: Pediatric asthma is a costly and complex disease with proven interventions to prevent exacerbations. Finding the patients at highest risk of exacerbations is paramount given limited resources. Insurance claims identify all outpatient, inpatient, emergency, pharmacy, and diagnostic services. The objective was to develop a risk score indicating the likelihood of asthma exacerbation within the next year based on prior utilization., Methods: A retrospective analysis of insurance claims for patients 2 to 18 years in a network in Massachusetts with 3 years of continuous enrollment in a commercial plan. Thirty-six potential predictors of exacerbation in the third year were assessed with a stepwise regression. Retained predictors were weighted relative to their contribution to asthma exacerbation risk and summed to create the Asthma Exacerbation Risk (AER) score., Results: In a cohort of 28,196 patients, there were 10 predictors associated with the outcome of having an asthma exacerbation in the next year that depend on age, meeting the Healthcare Effectiveness Data and Information Set persistent asthma criteria, fill patterns of asthma medications and oral steroids, counts of nonexacerbation outpatient visits, an exacerbation in the last 6 months, and whether spirometry was performed. The AER score is calculated monthly from a claims database to identify potential patients for an asthma home-visiting program., Conclusions: The AER score assigns a risk of exacerbation within the next 12 months using claims data to identify patients in need of preventive services., (Copyright © 2021 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: Inner-city children are disproportionately affected by asthma and sleep-disordered breathing (SDB). However, little is known about the association of SDB symptoms with asthma morbidity in this vulnerable population., Objective: Assess the relationship between snoring frequency and asthma morbidity., Methods: This study was part of the School Inner-City Asthma Study, a longitudinal prospective cohort study of children with persistent asthma who attended schools in the Northeast United States from 2008 to 2013. Participants had baseline assessments of asthma symptoms, snoring, and allergy status. Caregivers completed quarterly surveys for 12 months on symptoms of asthma, snoring, and health care outcomes. Snoring frequency (non-, rare-, sometimes-, habitual-snoring) and its relationship with asthma symptoms and asthma morbidity were assessed by mixed-effects models., Results: There were 1186 observations from 339 subjects. Mean age was 7.9 years; roughly half were male, and most were of minority race. Half were overweight or obese, and 65.5% had atopy. At initial snoring assessment, 24.8% reported habitual snoring, but report of snoring frequency varied over the study period. Multivariate analyses revealed increased odds of maximum asthma symptom days for habitual snoring compared with nonsnoring (1.58; 95% CI, 1.19-2.10; P < .002) and all other snoring categories. Habitual snoring was associated with greater odds of health care utilization (incidence rate ratio, 1.72; 95% CI, 1.10-2.69; P = .02) and worse asthma control (odds ratio, 1.49; 95% CI, 1.05-2.11; P = .03) compared with nonsnoring., Conclusions: Snoring is common among inner-city school-age children with asthma, and habitual snoring is associated with increased asthma symptom burden and health care utilization., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Importance: School and classroom allergens and particles are associated with asthma morbidity, but the benefit of environmental remediation is not known., Objective: To determine whether use of a school-wide integrated pest management (IPM) program or high-efficiency particulate air (HEPA) filter purifiers in the classrooms improve asthma symptoms in students with active asthma., Design, Setting, and Participants: Factorial randomized clinical trial of a school-wide IPM program and HEPA filter purifiers in the classrooms was conducted from 2015 to 2020 (School Inner-City Asthma Intervention Study). There were 236 students with active asthma attending 41 participating urban elementary schools located in the Northeastern US who were randomized to IPM by school and HEPA filter purifiers by classroom. The date of final follow-up was June 20, 2020., Interventions: The school-wide IPM program consisted of application of rodenticide, sealing entry points, trap placement, targeted cleaning, and brief educational handouts for school staff. Infestation was assessed every 3 months, with additional treatments as needed. Control schools received no IPM, cleaning, or education. Classroom portable HEPA filter purifiers were deployed and the filters were changed every 3 months. Control classrooms received sham HEPA filters that looked and sounded like active HEPA filter purifiers. Randomization was done independently (split-plot design), with matching by the number of enrolled students to ensure a nearly exact 1:1 student ratio for each intervention with 118 students randomized to each group. Participants, investigators, and those assessing outcomes were blinded to the interventions., Main Outcomes and Measures: The primary outcome was the number of symptom-days with asthma during a 2-week period. Symptom-days were assessed every 2 months during the 10 months after randomization., Results: Among the 236 students who were randomized (mean age, 8.1 [SD, 2.0] years; 113 [48%] female), all completed the trial. At baseline, the 2-week mean was 2.2 (SD, 3.9) symptom-days with asthma and 98% of the classrooms had detectable levels of mouse allergen. The results were pooled because there was no statistically significant difference between the 2 interventions (P = .18 for interaction). During a 2-week period, the mean was 1.5 symptom-days with asthma after use of the school-wide IPM program vs 1.9 symptom-days after no IPM across the school year (incidence rate ratio, 0.71 [95% CI, 0.38-1.33]), which was not statistically significantly different. During a 2-week period, the mean was 1.6 symptom-days with asthma after use of HEPA filter purifiers in the classrooms vs 1.8 symptom-days after use of sham HEPA filter purifiers across the school year (incidence rate ratio, 1.47 [95% CI, 0.79-2.75]), which was not statistically significantly different. There were no intervention-related adverse events., Conclusions and Relevance: Among children with active asthma, use of a school-wide IPM program or classroom HEPA filter purifiers did not significantly reduce symptom-days with asthma. However, interpretation of the study findings may need to consider allergen levels, particle exposures, and asthma symptoms at baseline., Trial Registration: ClinicalTrials.gov Identifier: NCT02291302.

Purpose: To investigate the characteristic thoracic multidetector computed tomography (MDCT) findings of dedicator of cytokinesis 8 (DOCK8) deficiency, a rare autosomal recessive form of hyperimmunoglobulin E syndrome, in children., Materials and Methods: All pediatric patients (age 18 y and below) with a known diagnosis of DOCK8 deficiency based on genetic testing who underwent thoracic MDCT studies from November 2004 to November 2020 were included. Two pediatric radiologists independently evaluated MDCT studies for the presence of thoracic abnormalities in the lung [ground-glass opacity (GGO), consolidation, pulmonary nodule, mass, cyst, and bronchiectasis], pleura (pleural effusion and pneumothorax), and mediastinum (lymphadenopathy). When a lung abnormality was present, laterality, distribution (upper, middle, and lower lung zone), and extent were also evaluated. When a pleural abnormality was identified, laterality and size of the abnormality were also assessed. When mediastinal lymphadenopathy was present, its location and size were also evaluated. Interobserver agreement between two independent reviewers was evaluated with κ statistics., Results: In all, 17 thoracic MDCT studies from 17 individual pediatric patients [5 males (29%) and 12 females (71%); mean age: 7.4 y; SD: 3.7; range: 1 to 13 y] comprised the final study population. Among 17 thoracic MDCT studies, 11 studies (65%) were performed with intravenous contrast (IV) and the remaining 6 MDCT studies (35%) were obtained without IV contrast. Bilateral bronchiectasis (11/17; 65%) with a middle lung zone predominance (8/11; 73%) was the most frequently detected lung abnormality, followed by GGO in 9/17 patients (53%). Among 11 contrast-enhanced MDCT studies, the majority (9 patients, 82%) had mediastinal lymphadenopathy. There was excellent interobserver κ agreement between 2 independent reviewers for detecting abnormalities on thoracic MDCT studies (κ>0.90)., Conclusion: Children with DOCK8 deficiency have characteristic thoracic MDCT findings, including bilateral bronchiectasis with a middle lung zone predominance, GGO, and mediastinal lymphadenopathy. When these characteristic thoracic MDCT findings are detected, although rare, DOCK8 deficiency should be considered as a possible underlying diagnosis in the pediatric population., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Almost half of all school-age children with bronchopulmonary dysplasia (BPD) have asthma-like symptoms and more suffer from lung function deficits. While air pollution and indoor respiratory irritants are known to affect high-risk populations of children, few studies have objectively evaluated environmental contributions to long-term respiratory morbidity in this population. This study aimed to examine the role of indoor environmental exposures on respiratory morbidity in children with BPD., Methods and Analysis: The Air quality, Environment and Respiratory Ouctomes in BPD (AERO-BPD) study is a prospective, single-centre observational study that will enrol a unique cohort of 240 children with BPD and carefully characterise participants and their indoor home environmental exposures. Measures of indoor air quality constituents will assess the relationship of nitrogen dioxide (NO 2 ), particulate matter (PM 2.5 ), nitric oxide (NO), temperature and humidity, as well as dust concentrations of allergens, with concurrently measured respiratory symptoms and lung function.Adaptations to the research protocol due to the SARS-CoV-2 pandemic included remote home environment and participant assessments., Ethics and Dissemination: Study protocol was approved by the Boston Children's Hospital Committee on Clinical Investigation. Dissemination will be in the form of peer-reviewed publications and participant information products., Trial Registration Number: NCT04107701., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Survivors of prematurity are at risk for abnormal childhood lung function. Few studies have addressed trajectories of lung function and risk factors for abnormal growth in childhood. This study aims to describe changes in lung function in a contemporary cohort of children born preterm followed longitudinally in pulmonary clinic for post-prematurity respiratory disease and to assess maternal and neonatal risk factors associated with decreased lung function trajectories., Methods: Observational cohort of 164 children born preterm ≤ 32 weeks gestation followed in pulmonary clinic at Boston Children's Hospital with pulmonary function testing. We collected demographics and neonatal history. We used multivariable linear regression to identify the impact of neonatal and maternal risk factors on lung function trajectories in childhood., Results: We identified 264 studies from 82 subjects with acceptable longitudinal FEV 1 data and 138 studies from 47 subjects with acceptable longitudinal FVC and FEV 1 /FVC data. FEV 1 % predicted and FEV 1 /FVC were reduced compared to childhood norms. Growth in FVC outpaced FEV 1 , resulting in an FEV 1 /FVC that declined over time. In multivariable analyses, longer duration of mechanical ventilation was associated with a lower rate of rise in FEV 1 % predicted and greater decline in FEV 1 /FVC, and postnatal steroid exposure in the NICU was associated with a lower rate of rise in FEV 1 and FVC % predicted. Maternal atopy and asthma were associated with a lower rate of rise in FEV 1 % predicted., Conclusions: Children with post-prematurity respiratory disease demonstrate worsening obstruction in lung function throughout childhood. Neonatal risk factors including exposure to mechanical ventilation and postnatal steroids, as well as maternal atopy and asthma, were associated with diminished rate of rise in lung function. These results may have implications for lung function trajectories into adulthood.

Rationale: It is unclear why select patients with moderate-to-severe asthma continue to lose lung function despite therapy. We hypothesized that participants with the smallest responses to parenteral corticosteroids have the greatest risk of undergoing a severe decline in lung function. Objectives: To evaluate corticosteroid-response phenotypes as longitudinal predictors of lung decline. Methods: Adults within the NHLBI SARP III (Severe Asthma Research Program III) who had undergone a course of intramuscular triamcinolone at baseline and at ≥2 annual follow-up visits were evaluated. Longitudinal slopes were calculated for each participant's post-bronchodilator FEV 1 % predicted. Categories of participant FEV 1 slope were defined: severe decline, >2% loss/yr; mild decline, >0.5-2.0% loss/yr; no change, 0.5% loss/yr to <1% gain/yr; and improvement, ≥1% gain/yr. Regression models were used to develop predictors of severe decline. Measurements and Main Results: Of 396 participants, 78 had severe decline, 91 had mild decline, 114 had no change, and 113 showed improvement. The triamcinolone-induced difference in the post-bronchodilator FEV 1 % predicted (derived by baseline subtraction) was related to the 4-year change in lung function or slope category in univariable models ( P  < 0.001). For each 5% decrement in the triamcinolone-induced difference the FEV1% predicted, there was a 50% increase in the odds of being in the severe decline group (odds ratio, 1.5; 95% confidence interval, 1.3-1.8), when adjusted for baseline FEV 1 , exacerbation history, blood eosinophils and body mass index. Conclusions: Failure to improve the post-bronchodilator FEV 1 after a challenge with parenteral corticosteroids is an evoked biomarker for patients at risk for a severe decline in lung function.

Background: Asthma is among the most common chronic diseases of children in the United States (US). Mold exposures have been linked to asthma development and exacerbation. In homes, mold exposures have been quantified using the Environmental Relative Moldiness Index (ERMI), and higher home ERMI values have been linked to occupant asthma., Objective: In this analysis of the School Inner-City Asthma Study (SICAS), we aimed to evaluate the ERMI's applicability to measuring mold in schools compared with homes and to examine the prevalence of asthma in relationship to students' demographics and the physical characteristics of school buildings., Methods: Northeastern US schools (n = 32) and homes (n = 33) were selected, and the 36 ERMI molds were quantified in a dust sample from each classroom (n = 114) or home. School building characteristics data were collected from SICAS. Asthma prevalence and student demographics data were obtained from government websites. Linear regression and mixed models were fit to assess the association of the current asthma prevalence and physical characteristics of the school, make-up of the student body, and the ERMI metric., Results: Levels of outdoor group 2 molds were significantly (P < .01) greater in schools compared with homes. The presence of air-conditioning in school buildings correlated significantly (P = .02) with lower asthma prevalence., Conclusion: The prevalence of asthma in student bodies is associated with many factors in schools and homes., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: Psychological comorbidities have been associated with asthma in adults and children, but have not been studied in a population of children with severe asthma. The aim of this study was to test the hypothesis that symptoms of anxiety or depression are highly prevalent in pediatric severe asthma and negatively effects asthma control., Methods: Longitudinal assessments of anxiety or depression symptoms (Patient Health Questionnaire-4 [PHQ-4]), asthma control (Asthma Control Test [ACT]), and lung function were performed in a single-center pediatric severe asthma clinic. Participant data were collected during routine clinical care. Primary outcomes were ACT and forced expiratory volume in 1 s per forced vital capacity (FEV1/FVC)., Results: Among 43 subjects (with total 93 observations), 58.1% reported at least one anxious or depressive symptom and 18.6% had a PHQ-4 more than 2, the threshold for an abnormal test result. After adjusting for age, sex, race, and asthma medication step, there was a significant reduction in ACT for girls with PHQ-4 more than 2 (adjusted mean [SE] ACT for PHQ-4 > 2: 13.64 [0.59], ACT for PHQ-4 ≤ 2: 20.64 [1.25], p = .02) but not boys. Moreover, there was a significant differential effect of mental health impairment for girls than boys. ACT for girls with PHQ more than 2: 13.64 (0.59) compared with boys with PHQ-4 more than 2: 17.82 (0.95), adjusted mean difference ACT by sex = 4.18 points; 95% confidence interval, 0.63-7.73; p = .033. In adjusted models, there was no association between PHQ-4 more than 2 and FEV1/FVC., Conclusions: Symptoms of anxiety and depression are common. In children with severe asthma, a PHQ-4 score more than 2 is associated with worse asthma symptom control in girls, but not boys., (© 2020 Wiley Periodicals LLC.)

Asthma remains one of the most important challenges to pediatric public health in the US. A large majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization, which remains a pivotal risk factor associated with the development of persistent, progressive asthma throughout life. In individuals with a tendency toward Type 2 inflammation, sensitization and exposure to high concentrations of offending allergens is associated with increased risk for development of, and impairment from, asthma. The cascade of biological responses to allergens is primarily mediated through IgE antibodies and their production is further stimulated by IgE responses to antigen exposure. In addition, circulating IgE impairs innate anti-viral immune responses. The latter effect could magnify the effects of another early life exposure associated with increased risk of the development of asthma - viral infections. Omalizumab binds to circulating IgE and thus ablates antigen signaling through IgE-related mechanisms. Further, it has been shown restore IFN-α response to rhinovirus and to reduce asthma exacerbations during the viral season. We therefore hypothesized that early blockade of IgE and IgE mediated responses with omalizumab would prevent the development and reduce the severity of asthma in those at high risk for developing asthma. Herein, we describe a double-blind, placebo-controlled trial of omalizumab in 2-3 year old children at high risk for development of asthma to prevent the development and reduce the severity of asthma. We describe the rationale, methods, and lessons learned in implementing this potentially transformative trial aimed at prevention of asthma., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Globally, exposure to ambient air pollutants is responsible for premature mortality and is implicated in the development and exacerbation of several acute and chronic lung disease across all ages. In this article, we discuss the source apportionment of ambient pollutants and the respiratory health effects in humans. We specifically discuss the evidence supporting ambient pollution in the development of asthma and chronic obstructive pulmonary disease and acute exacerbations of each condition. Practical advice is given to health care providers in how to promote a healthy environment and advise patients with chronic conditions to avoid unsafe air quality., Competing Interests: Disclosure None of the authors have any commercial/financial conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)